ES2260457T3 - Procedimiento para la produccion de 4-amino-2,5- bisheterociclilquinazlinas. - Google Patents
Procedimiento para la produccion de 4-amino-2,5- bisheterociclilquinazlinas.Info
- Publication number
- ES2260457T3 ES2260457T3 ES02745749T ES02745749T ES2260457T3 ES 2260457 T3 ES2260457 T3 ES 2260457T3 ES 02745749 T ES02745749 T ES 02745749T ES 02745749 T ES02745749 T ES 02745749T ES 2260457 T3 ES2260457 T3 ES 2260457T3
- Authority
- ES
- Spain
- Prior art keywords
- ring
- formula
- alkyl
- compound
- alkoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 22
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 11
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 11
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 239000012453 solvate Substances 0.000 claims abstract description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 8
- 239000011734 sodium Substances 0.000 claims abstract description 8
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 8
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000003880 polar aprotic solvent Substances 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000001555 benzenes Chemical class 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 239000000725 suspension Substances 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- -1 2-pyrimidyl Chemical group 0.000 description 8
- QHJVAZDEOBKUGE-UHFFFAOYSA-N 6-amino-3,4-dimethoxy-2-pyridin-2-ylbenzonitrile Chemical compound COC1=CC(N)=C(C#N)C(C=2N=CC=CC=2)=C1OC QHJVAZDEOBKUGE-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 6
- 229940011051 isopropyl acetate Drugs 0.000 description 6
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 6
- MTAXDWONEJVCNF-UHFFFAOYSA-N n-(2-cyano-3,4-dihydro-1h-isoquinolin-5-yl)methanesulfonamide Chemical compound C1N(C#N)CCC2=C1C=CC=C2NS(=O)(=O)C MTAXDWONEJVCNF-UHFFFAOYSA-N 0.000 description 6
- OLYXPBZBZBVRGD-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=NC(N)=C2C=1C1=CC=CC=N1 OLYXPBZBZBVRGD-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 150000003246 quinazolines Chemical class 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 3
- LFSYMBZTFIVRSE-UHFFFAOYSA-N 6-amino-2-iodo-3,4-dimethoxybenzonitrile Chemical compound COC1=CC(N)=C(C#N)C(I)=C1OC LFSYMBZTFIVRSE-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 3
- OJPDDQSCZGTACX-UHFFFAOYSA-N 2-[n-(2-hydroxyethyl)anilino]ethanol Chemical compound OCCN(CCO)C1=CC=CC=C1 OJPDDQSCZGTACX-UHFFFAOYSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012455 biphasic mixture Substances 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 2
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- KRIWIRSMQRQYJG-DLBZAZTESA-N (2s,3s)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol Chemical compound C=1C(N[C@@H](CO)[C@H](O)CO)=NC2=C(C(C)C)C=NN2C=1NCC1=CC=CC=C1 KRIWIRSMQRQYJG-DLBZAZTESA-N 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- ROAHGYIWORDPKO-UHFFFAOYSA-N 2-iodo-3,4-dimethoxy-6-nitrobenzonitrile Chemical compound COC1=CC([N+]([O-])=O)=C(C#N)C(I)=C1OC ROAHGYIWORDPKO-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 229920003189 Nylon 4,6 Polymers 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 230000017525 heat dissipation Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- QBXFQTLJZAJJQN-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-5-yl)methanesulfonamide Chemical compound C1NCCC2=C1C=CC=C2NS(=O)(=O)C QBXFQTLJZAJJQN-UHFFFAOYSA-N 0.000 description 1
- VIXRVBRUSDQWJD-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-5-yl)methanesulfonamide;hydrochloride Chemical compound Cl.C1NCCC2=C1C=CC=C2NS(=O)(=O)C VIXRVBRUSDQWJD-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- YRPMGVDYZGWOPA-UHFFFAOYSA-N pyridin-2-yloxyboronic acid Chemical compound OB(O)OC1=CC=CC=N1 YRPMGVDYZGWOPA-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical class C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0118752.5A GB0118752D0 (en) | 2001-08-01 | 2001-08-01 | Process for the production of quinazolines |
| GB0118752 | 2001-08-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2260457T3 true ES2260457T3 (es) | 2006-11-01 |
Family
ID=9919612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02745749T Expired - Lifetime ES2260457T3 (es) | 2001-08-01 | 2002-07-19 | Procedimiento para la produccion de 4-amino-2,5- bisheterociclilquinazlinas. |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7026479B2 (cs) |
| EP (1) | EP1412331B1 (cs) |
| JP (1) | JP2005501054A (cs) |
| KR (1) | KR20040019097A (cs) |
| CN (1) | CN1533378A (cs) |
| AP (1) | AP1299A (cs) |
| AR (1) | AR036204A1 (cs) |
| AT (1) | ATE323677T1 (cs) |
| BR (1) | BR0211670A (cs) |
| CA (1) | CA2451075A1 (cs) |
| CZ (1) | CZ2004151A3 (cs) |
| DE (1) | DE60210778T2 (cs) |
| DO (1) | DOP2002000443A (cs) |
| EG (1) | EG23204A (cs) |
| ES (1) | ES2260457T3 (cs) |
| GB (1) | GB0118752D0 (cs) |
| HN (1) | HN2002000197A (cs) |
| HU (1) | HUP0401573A3 (cs) |
| IL (1) | IL158998A0 (cs) |
| MX (1) | MXPA04000978A (cs) |
| PA (1) | PA8550301A1 (cs) |
| PE (1) | PE20030346A1 (cs) |
| PL (1) | PL368520A1 (cs) |
| RU (1) | RU2261861C1 (cs) |
| UY (1) | UY27399A1 (cs) |
| WO (1) | WO2003011829A1 (cs) |
| ZA (1) | ZA200309043B (cs) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003249212C1 (en) | 2002-07-15 | 2011-10-27 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| EP3329918B1 (en) | 2003-09-26 | 2022-05-25 | Exelixis, Inc. | C-met modulators and methods of use |
| PT1746999E (pt) * | 2004-05-06 | 2012-01-11 | Warner Lambert Co | 4-fenilamino-quinazolin-6-il-amidas |
| PL2054416T3 (pl) * | 2006-08-04 | 2011-05-31 | Merz Pharma Gmbh & Co Kgaa | Podstawione pirazolopirymidyny, sposób ich wytwarzania oraz ich zastosowanie w medycynie |
| PT2387563E (pt) | 2009-01-16 | 2013-03-25 | Exelixis Inc | Sal de malato de n-(4-{[6,7-bis(metiloxi)quinolin-4- il]oxi}fenil)-n¿-(4-fluorofenil)ciclopropano-1,1-dicarboxamida, e suas formas cristalinas para o tratamento de cancro |
| KR101841003B1 (ko) | 2009-03-18 | 2018-03-22 | 리스버로직스 코퍼레이션 | 신규한 소염제 |
| IN2012DN00352A (cs) * | 2009-06-16 | 2015-08-21 | Bikam Pharmaceuticals Inc | |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| EP2785346A4 (en) | 2011-11-30 | 2015-04-29 | Bikam Pharmaceuticals Inc | OPSINBINDING LIGANDS, COMPOSITIONS THEREOF, AND METHOD OF USE THEREOF |
| PT2906531T (pt) * | 2012-10-15 | 2018-02-06 | Resverlogix Corp | Compostos úteis na síntese de compostos de benzamida |
| EP3268007B1 (en) | 2015-03-13 | 2022-11-09 | Resverlogix Corp. | Compositions and therapeutic methods for the treatment of complement-associated diseases |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8719378D0 (en) * | 1987-08-15 | 1987-09-23 | Pfizer Ltd | Antiarrythmic agents |
| WO1998030562A1 (fr) * | 1997-01-09 | 1998-07-16 | Terumo Kabushiki Kaisha | Nouveaux derives d'amide et intermediaires utilises pour leur synthese |
| GB9700504D0 (en) * | 1997-01-11 | 1997-02-26 | Pfizer Ltd | Pharmaceutical compounds |
-
2001
- 2001-08-01 GB GBGB0118752.5A patent/GB0118752D0/en not_active Ceased
-
2002
- 2002-07-11 PA PA20028550301A patent/PA8550301A1/es unknown
- 2002-07-19 IL IL15899802A patent/IL158998A0/xx unknown
- 2002-07-19 CN CNA028143256A patent/CN1533378A/zh active Pending
- 2002-07-19 KR KR10-2004-7001513A patent/KR20040019097A/ko not_active Ceased
- 2002-07-19 HU HU0401573A patent/HUP0401573A3/hu unknown
- 2002-07-19 MX MXPA04000978A patent/MXPA04000978A/es active IP Right Grant
- 2002-07-19 ES ES02745749T patent/ES2260457T3/es not_active Expired - Lifetime
- 2002-07-19 JP JP2003517021A patent/JP2005501054A/ja active Pending
- 2002-07-19 EP EP02745749A patent/EP1412331B1/en not_active Expired - Lifetime
- 2002-07-19 BR BR0211670-7A patent/BR0211670A/pt not_active IP Right Cessation
- 2002-07-19 US US10/199,755 patent/US7026479B2/en not_active Expired - Fee Related
- 2002-07-19 AT AT02745749T patent/ATE323677T1/de not_active IP Right Cessation
- 2002-07-19 CA CA002451075A patent/CA2451075A1/en not_active Abandoned
- 2002-07-19 DE DE60210778T patent/DE60210778T2/de not_active Expired - Fee Related
- 2002-07-19 RU RU2004102692/04A patent/RU2261861C1/ru not_active IP Right Cessation
- 2002-07-19 PL PL02368520A patent/PL368520A1/xx not_active Application Discontinuation
- 2002-07-19 CZ CZ2004151A patent/CZ2004151A3/cs unknown
- 2002-07-19 WO PCT/IB2002/002872 patent/WO2003011829A1/en active IP Right Grant
- 2002-07-23 DO DO2002000443A patent/DOP2002000443A/es unknown
- 2002-07-26 PE PE2002000678A patent/PE20030346A1/es not_active Application Discontinuation
- 2002-07-29 UY UY27399A patent/UY27399A1/es not_active Application Discontinuation
- 2002-07-29 HN HN2002000197A patent/HN2002000197A/es unknown
- 2002-07-29 EG EG2002070853A patent/EG23204A/xx active
- 2002-07-31 AR ARP020102914A patent/AR036204A1/es unknown
- 2002-08-01 AP APAP/P/2002/002602A patent/AP1299A/en active
-
2003
- 2003-11-20 ZA ZA200309043A patent/ZA200309043B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1412331A1 (en) | 2004-04-28 |
| KR20040019097A (ko) | 2004-03-04 |
| DOP2002000443A (es) | 2003-02-15 |
| US20030100753A1 (en) | 2003-05-29 |
| ATE323677T1 (de) | 2006-05-15 |
| EP1412331B1 (en) | 2006-04-19 |
| UY27399A1 (es) | 2003-02-28 |
| BR0211670A (pt) | 2004-07-13 |
| HUP0401573A2 (hu) | 2005-01-28 |
| HUP0401573A3 (en) | 2005-06-28 |
| PL368520A1 (en) | 2005-04-04 |
| US7026479B2 (en) | 2006-04-11 |
| IL158998A0 (en) | 2004-05-12 |
| AP1299A (en) | 2004-09-06 |
| AR036204A1 (es) | 2004-08-18 |
| CN1533378A (zh) | 2004-09-29 |
| EG23204A (en) | 2004-07-31 |
| PE20030346A1 (es) | 2003-04-05 |
| MXPA04000978A (es) | 2004-04-20 |
| JP2005501054A (ja) | 2005-01-13 |
| DE60210778D1 (de) | 2006-05-24 |
| RU2004102692A (ru) | 2005-07-10 |
| RU2261861C1 (ru) | 2005-10-10 |
| PA8550301A1 (es) | 2003-09-05 |
| ZA200309043B (en) | 2004-11-22 |
| GB0118752D0 (en) | 2001-09-26 |
| CA2451075A1 (en) | 2003-02-13 |
| CZ2004151A3 (cs) | 2005-01-12 |
| HN2002000197A (es) | 2003-02-27 |
| DE60210778T2 (de) | 2007-01-04 |
| AP2002002602A0 (en) | 2002-09-30 |
| WO2003011829A1 (en) | 2003-02-13 |
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